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Genetic markers of dopaminergic transmission predict performance for older males but not females.

ABSTRACT: Mobility and memory declines with aging can limit independence. Several single-nucleotide polymorphisms have been associated with cognitive performance, but studies investigating motor function are scant. We examined 4 single-nucleotide polymorphisms involved in dopaminergic metabolism: BDNF (Val66Met), DRD3 (Ser9Gly), DBH (C>T), and COMT (Val158Met) for their relationship to motor and cognitive function in healthy older adults (n = 4605 and n = 7331) who participated in the U.S. Health and Retirement Study. Individuals with genotypes associated with reduced dopamine metabolism exhibited poorer balance and memory. We found the most pronounced effects in the oldest participants (aged 85+ years), supporting the notion that age-related declines in dopamine availability contribute to magnified genotype effects with advancing age. Moreover, males demonstrated stronger associations than did females between a number of beneficial dopamine alleles and cognitive scores, suggesting that sex differences in dopaminergic transmission interact with genotype to influence performance. These findings point to common genetic variants related to dopaminergic metabolism that characterizes individual differences in motor and cognitive function in older adults.

SUBMITTER: Hupfeld KE

PROVIDER: S-EPMC5924602 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Genetic markers of dopaminergic transmission predict performance for older males but not females.

Hupfeld Kathleen E KE Vaillancourt David E DE Seidler Rachael D RD

Neurobiology of aging 20180210

Mobility and memory declines with aging can limit independence. Several single-nucleotide polymorphisms have been associated with cognitive performance, but studies investigating motor function are scant. We examined 4 single-nucleotide polymorphisms involved in dopaminergic metabolism: BDNF (Val66Met), DRD3 (Ser9Gly), DBH (C>T), and COMT (Val158Met) for their relationship to motor and cognitive function in healthy older adults (n = 4605 and n = 7331) who participated in the U.S. Health and Reti ...[more]

PMID: 29525179

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Project description:Moral behavior has been a key topic of debate for philosophy and psychology for a long time. In recent years, thanks to the development of novel methodologies in cognitive sciences, the question of how we make moral choices has expanded to the study of neurobiological correlates that subtend the mental processes involved in moral behavior. For instance, in vivo brain imaging studies have shown that distinct patterns of brain neural activity, associated with emotional response and cognitive processes, are involved in moral judgment. Moreover, while it is well-known that responses to the same moral dilemmas differ across individuals, to what extent this variability may be rooted in genetics still remains to be understood. As dopamine is a key modulator of neural processes underlying executive functions, we questioned whether genetic polymorphisms associated with decision-making and dopaminergic neurotransmission modulation would contribute to the observed variability in moral judgment. To this aim, we genotyped five genetic variants of the dopaminergic pathway [rs1800955 in the dopamine receptor D4 (DRD4) gene, DRD4 48 bp variable number of tandem repeat (VNTR), solute carrier family 6 member 3 (SLC6A3) 40 bp VNTR, rs4680 in the catechol-O-methyl transferase (COMT) gene, and rs1800497 in the ankyrin repeat and kinase domain containing 1 (ANKK1) gene] in 200 subjects, who were requested to answer 56 moral dilemmas. As these variants are all located in genes belonging to the dopaminergic pathway, they were combined in multilocus genetic profiles for the association analysis. While no individual variant showed any significant effects on moral dilemma responses, the multilocus genetic profile analysis revealed a significant gender-specific influence on human moral acceptability. Specifically, those genotype combinations that improve dopaminergic signaling selectively increased moral acceptability in females, by making their responses to moral dilemmas more similar to those provided by males. As females usually give more emotionally-based answers and engage the "emotional brain" more than males, our results, though preliminary and therefore in need of replication in independent samples, suggest that this increase in dopamine availability enhances the cognitive and reduces the emotional components of moral decision-making in females, thus favoring a more rationally-driven decision process.

Dataset Information

Genetic markers of dopaminergic transmission predict performance for older males but not females.

Publications

Genetic markers of dopaminergic transmission predict performance for older males but not females.

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